Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. METHODS: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. RESULTS: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52-0.99]; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; P=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; P=0.57) in the influenza vaccine and placebo groups, respectively. CONCLUSIONS: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.

Epidemiology of paediatric Middle East respiratory syndrome coronavirus and implications for the control of coronavirus virus disease 2019.

AIM: To compare the clinical features of Middle East respiratory syndrome coronavirus (MERS-CoV) infection between paediatric and adult cases. METHODS: Using multiple public data sources, we created an enhanced open-source surveillance dataset of all MERS-CoV cases between 20 September 2012 and 31 December 2018 in Saudi Arabia including available risk factor data. RESULTS: Of the 1791 cases of MERS-CoV identified, 30 cases (1.7%) were aged under 18 years and 1725 cases (96.3%) were aged 18 years and over. Three paediatric cases were fatal, aged 0, 2 and 15 years. The odds of asymptomatic MERS-CoV infection among cases under 18 years (n = 10/23; 44%) was significantly higher (odds ratio (OR) = 4.98; 95% confidence interval (CI): 2.15-11.51; P = 0.001) compared to adults (n = 199/1487; 13%). The odds of hospitalisation were significantly lower (OR = 0.17; 95% CI: 0.08-0.39; P < 0.001) among cases under 18 years (n = 12/24; 50%) compared to adults (n = 1231/1443; 85%). Children were more likely to have a known source of exposure compared to adults (OR = 2.68; 95% CI: 1.29-5.56; P = 0.008). CONCLUSIONS: Clinically severe illness is less common in children, although death can occur, and the proportion of paediatric cases (1.7%) is similar to that reported for COVID-19. Age-specific differences in the clinical presentation of MERS-CoV cases could have implications for transmission for other betacoronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Children may be at risk within the household with an infected adult. More studies are required on the role of children in transmission of betacoronaviruses.

Application of a Risk Analysis Tool to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreak in Saudi Arabia.

The Grunow-Finke assessment tool (GFT) is an accepted scoring system for determining likelihood of an outbreak being unnatural in origin. Considering its high specificity but low sensitivity, a modified Grunow-Finke tool (mGFT) has been developed with improved sensitivity. The mGFT has been validated against some past disease outbreaks, but it has not been applied to ongoing outbreaks. This study is aimed to score the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia using both the original GFT and mGFT. The publicly available data on human cases of MERS-CoV infections reported in Saudi Arabia (2012-2018) were sourced from the FluTrackers, World Health Organization, Saudi Ministry of Health, and published literature associated with MERS outbreaks investigations. The risk assessment of MERS-CoV in Saudi Arabia was analyzed using the original GFT and mGFT criteria, algorithms, and thresholds. The scoring points for each criterion were determined by three researchers to minimize the subjectivity. The results showed 40 points of total possible 54 points using the original GFT (likelihood: 74%), and 40 points of a total possible 60 points (likelihood: 67%) using the mGFT, both tools indicating a high likelihood that human MERS-CoV in Saudi Arabia is unnatural in origin. The findings simply flag unusual patterns in this outbreak, but do not prove unnatural etiology. Proof of bioattacks can only be obtained by law enforcement and intelligence agencies. This study demonstrated the value and flexibility of the mGFT in assessing and predicting the risk for an ongoing outbreak with simple criteria.